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Choosing Your Fate

During differentiation, cell lineages must choose between different alternate fates. Hong et al. provide evidence that a protein known as TAZ (for transcriptional co-activator with PDZ-binding motif) is a key regulator that helps determine the fate of mesenchymal stem cells that can differentiate into osteoblasts or adipocytes. TAZ contains a protein interaction domain that binds to Pro-Pro-X-Tyr motifs (where X represents any amino acid). Two transcription factors that control differentiation of mesenchymal stem cells, Runx2 and PPARγ, contain such a motif in their activation domains. In tissue culture and in zebrafish embryos, TAZ promotes formation of osteoblasts (by cooperating with Runx2) and inhibits differentiation of adipocytes (by antagonizing the effects of PPARγ).